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Dissertation final 05-08-17.pdf (30.99 MB)

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Regulation of Suprachiasmatic Nucleus and Hippocampal Cellular Activity as a Function of Circadian Signaling

Alzate Correa, Diego Fernando
http://orcid.org/0000-0001-5750-0207
http://rave.ohiolink.edu/etdc/view?acc_num=osu1494196688129828

Abstract Details

2017, Doctor of Philosophy, Ohio State University, Pharmaceutical Sciences.
Circadian rhythms are defined as oscillations in biological processes with a period similar to the 24 hour period of the earth’s rotation. In mammals, circadian rhythms are controlled by the suprachiasmatic nucleus (SCN), a hypothalamic structure working as a central pacemaker that drives the circadian rhythms that are expressed in other brain regions, as well as throughout the rest of the organism. The manifestation of circadian rhythms is structured by the presence in nearly all cells of a molecular clock, a transcriptional and translational feedback loop that directs the timing of numerous cellular processes. Although endogenous circadian rhythms are self-sustained, entrainment of the SCN circadian clock is induced by diverse environmental factors in order to maintain a synchrony with external geophysical cycles, with light being recognized as one of the most robust entrainment signals. Here, I first present a study aimed at describing genome-wide expression changes in the SCN triggered by light inputs in the SCN (Chapter2). In this respect, previous studies have shown that the effects of light in the SCN are time-of-day specific, resulting from differential responses in specific neuronal signaling pathways. In particular, activation of the mitogen-activated protein kinases/ extracellular signal–regulated kinases (MAPK/ERK) signaling pathway in the SCN couples photic stimuli with circadian entrainment through changes in gene expression. Using microarray analysis and pharmacological interventions, I describe here the number and nature of transcripts induced by light at multiple points of the circadian cycle, with a particular emphasis on the subgroup of light-induced genes whose expression is modulated by the activation of the MAPK/ERK signaling pathway. This examination is followed by studies aimed to determine the influence of circadian rhythms on the function of the hippocampus. First, I assess the role of circadian rhythms in the formation and retrieval of contextual memories, a task mediated by the hippocampus (Chapter 3). There is a known relationship between circadian rhythms and memory formation, but the cellular and molecular mechanisms linking them are not fully understood. Here, the recruitment and activation of particular neuronal ensembles, essential for the encoding and retrieval of contextual memories, is correlated with specific phases of the circadian clock. Finally, hippocampal function is also examined here by the modulation of adult neural stem/progenitor cell function (Chapter 4). The circadian clock is expressed in embryonic and mature tissues, and regulates the proliferation and differentiation rates of tissue-specific stem cells. Here, I identify the expression and circadian oscillation of the molecular clock in this particular population of stem cells in the adult hippocampus, and then evaluate the changes observed in proliferation and differentiation rates of the stem/progenitor cell population as a consequence of a genetic disruption of the molecular clock.
Kari Hoyt, PhD (Advisor)
Karl Obrietan, PhD (Other)
144 p.
Neurobiology; Neurosciences; Pharmacology; Pharmacy Sciences
circadian rhythms; entrainment; light-induced entrainment; suprachiasmatic nucleus; transcriptome; microarray; hippocampus; contextual fear conditioning; memory; adult neurogenesis

Recommended Citations

Citations

  • Alzate Correa, D. F. (2017). Regulation of Suprachiasmatic Nucleus and Hippocampal Cellular Activity as a Function of Circadian Signaling [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1494196688129828

    APA Style (7th edition)

  • Alzate Correa, Diego. Regulation of Suprachiasmatic Nucleus and Hippocampal Cellular Activity as a Function of Circadian Signaling. 2017. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1494196688129828.

    MLA Style (8th edition)

  • Alzate Correa, Diego. "Regulation of Suprachiasmatic Nucleus and Hippocampal Cellular Activity as a Function of Circadian Signaling." Doctoral dissertation, Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1494196688129828

    Chicago Manual of Style (17th edition)

osu1494196688129828
61
© 2017, some rights reserved.Creative Commons License Regulation of Suprachiasmatic Nucleus and Hippocampal Cellular Activity as a Function of Circadian Signaling by Diego Fernando Alzate Correa is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by The Ohio State University and OhioLINK.